Annexin A2 promotes phagophore assembly by enhancing Atg16L+ vesicle biogenesis and homotypic fusion

Kateryna Morozova, Sunandini Sidhar, Valerio Zolla, Cristina C. Clement, Brian Scharf, Zoe Verzani, Antonio Diaz, Jorge N. Larocca, Katherine A. Hajjar, Ana Maria Cuervo, Laura Santambrogio

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Abstract

Plasma membrane budding of Atg-16L-positive vesicles represents a very early event in the generation of the phagophore and in the process of macroautophagy. Here we show that the membrane curvature-inducing protein annexin A2 contributes to the formation of these vesicles and their fusion to form phagophores. Ultrastructural, proteomic and FACS analyses of Atg16L-positive vesicles reveal that 30% of Atg16L-positive vesicles are also annexin A2-positive. Lipidomic analysis of annexin A2-deficient mouse cells indicates that this protein plays a role in recruiting phosphatidylserine and phosphatidylinositides to Atg16L-positive vesicles. Absence of annexin A2 reduces both vesicle formation and homotypic Atg16L vesicle fusion. Ultimately, a reduction in LC3 flux and dampening of macroautophagy are observed in dendritic cells from Anxa2-/- mice. Together, our analyses highlight the importance of annexin A2 in vesiculation of a population of Atg16L-positive structures from the plasma membrane, and in their homotypic fusion to form phagophore structures.

Original languageEnglish (US)
Article number5856
JournalNature communications
Volume6
DOIs
StatePublished - Jan 2015

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Morozova, K., Sidhar, S., Zolla, V., Clement, C. C., Scharf, B., Verzani, Z., Diaz, A., Larocca, J. N., Hajjar, K. A., Cuervo, A. M., & Santambrogio, L. (2015). Annexin A2 promotes phagophore assembly by enhancing Atg16L+ vesicle biogenesis and homotypic fusion. Nature communications, 6, [5856]. https://doi.org/10.1038/ncomms6856